Gas Exchanger and Artificial Lung

ABSTRACT

Blood or other fluids can be caused to interact with a gas by providing a plurality of fluid flow channels that are surrounded by nanotubes, each of the channels having an inflow end and an outflow end, wherein each of the channels is wide enough for the blood to flow through, and wherein the nanotubes are spaced close enough to each other to retain the fluid within the channels when the blood is flowing through the channels. The fluid is then passed through the through the channels while a gas is passed through the spaces between the nanotubes outside the fluid flow channels. This permits the gas to interact with the fluid in the channels.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of application Ser. No.14/331,608, filed Jul. 15, 2014, which claims the benefit of U.S.Provisional Application 61/846,888, filed Jul. 16, 2013. Each of theabove-identified applications is incorporated herein by reference in itsentirety.

BACKGROUND

The main function of the lung is to exchange gasses between the ambientair and the blood. Within this framework O₂ is transferred from theenvironment to the blood while CO₂ is eliminated from the body.

In a normal resting human these processes are associated with an O₂input of about 200-250 cm³/min and an output of about the same amount ofCO₂. This exchange is made through a surface area of 50-100 m² of a0.5-1 μm thick biological membrane separating the alveolar air from thepulmonary blood. This process is associated with the flow of similarvolumes of blood and air—about 5 Liter/min. At the given flow rate theblood is in “contact” with the membrane through which diffusion takesplace for a time period of ⅓-⅕ sec.

In natural systems such as the lung the gas exchange is achieved bydiffusion taking place across a thin biological membrane separating twocompartments: the gases in the lung alveoli and the gases contained inthe blood of the lung capillaries. The gases in the alveolar compartmentare maintained at a composition close to that of ambient air or gas bymoving the air or gases in and out of the lungs by respiratorymovements. The gas exchange is achieved by diffusion through the surfacearea of the exchange membrane that is extremely large—about 70 m². Thedriving force for diffusion of gases into and out of the blood ismaintained by a very large blood flow through the lung capillaries.

Nanotubes (“NT”) are inert cylindrical structures having diameters ofabout 1-100 nm. In the case of carbon NT they are constructed of one ormore layers of hexagonal carbon atom mesh. Their length can reach valuesin the cm range. FIG. 1A depicts a single wall NT made of carbon. Atthis time, NTs are well-known structures, and ways to make NTs are alsowell known. FIG. 1B depicts a scanning electron microscope photo of amatrix of parallel aligned carbon nanotubes.

Nanofibers are similar structures made out of carbon, silicon, etc. andare also commercially available. Nanofibers are defined as fibers withdiameters less than 100 nanometers (see ref 1). In the textile industry,this definition is often extended to include fibers as large as 1000 nmdiameter (see ref 2). Carbon nanofibers are graphitized fibers producedby catalytic synthesis. Inorganic nanofibers (sometimes called ceramicnanofibers) can be prepared from various kinds of inorganic substances,the most frequently mentioned ceramic materials with nanofibermorphology are titanium dioxide (TiO2), silicon dioxide (SiO2),zirconium dioxide (ZrO2), aluminum oxide (Al2O3), lithium titanate(Li4Ti5O12), titanium nitride (TiN) or platinum (Pt).

SUMMARY OF THE INVENTION

One aspect of the invention is directed to a gas exchange unit forprocessing blood that includes blood cells and plasma. This gas exchangeunit includes a substrate having a first side and a second side. Aplurality of nanotubes are disposed on the second side of the substratewith spaces between the nanotubes, and the nanotubes are disposed on thesubstrate in a configuration that leaves a plurality of blood flowchannels that are surrounded by the nanotubes, each of the channelshaving an inflow end and an outflow end. Each of the channels is wideenough for the blood to flow through, and the nanotubes are spaced closeenough to each other to retain the plasma within the channels when theblood is flowing through the channels. The substrate has a plurality ofperforations that extend between the first side of the substrate and thesecond side of the substrate, each of the perforations being alignedwith a respective one of the channels. This gas exchange unit alsoincludes a blood inlet configured to supply blood to the first side ofthe substrate, wherein the blood inlet is in fluid communication withthe perforations such that blood that arrives via the blood inlet willflow through the perforations and continue on through the channels. Italso includes a blood outlet configured to accept blood that arrivesfrom the outflow end of the channels. It also includes a housingconfigured to house the substrate and the array of nanotubes, thehousing having a gas inlet configured to route a gas into the spacesbetween the nanotubes and a gas outlet configured to route the gas awayfrom the spaces between the nanotubes.

In some embodiments, each of the nanotubes is perpendicular to thesubstrate and each of the channels is perpendicular to the substrate. Insome embodiments, the nanotubes are disposed on the substrate in anarray configuration, with a plurality of voids in the array, whereineach of the voids corresponds to a respective channel. In someembodiments, each of the channels has a diameter between 2 and 500 μm.In some embodiments, the nanotubes have a diameter between 5 and 20 nm.In some embodiments, the nanotubes are spaced on centers that arebetween 1.5 times the diameter of the nanotubes and 5 times the diameterof the nanotubes. In some embodiments, each of the nanotubes isperpendicular to the substrate, each of the channels is perpendicular tothe substrate, each of the channels has a diameter between 2 and 500 μm,and the nanotubes have a diameter between 5 and 20 nm. The nanotubes maybe spaced on centers that are between 1.5 times the diameter of thenanotubes and 5 times the diameter of the nanotubes. In someembodiments, the nanotubes are disposed on the substrate in an arrayconfiguration, with a plurality of voids in the array, wherein each ofthe voids corresponds to a respective channel.

Another aspect of the invention is directed to a gas exchanger forprocessing blood that Includes blood cells and plasma. This gasexchanger includes a plurality of gas exchange units. Each of these gasexchange units includes (a) a substrate having a first side and a secondside, (b) a plurality of nanotubes disposed on the second side of thesubstrate with spaces between the nanotubes, wherein the nanotubes aredisposed on the substrate in a configuration that leaves a plurality ofblood flow channels that are surrounded by the nanotubes. Each of thechannels has an inflow end and an outflow end, and each of the channelsis wide enough for the blood to flow through. The nanotubes are spacedclose enough to each other to retain the plasma within the channels whenthe blood is flowing through the channels. The substrate has a pluralityof perforations that extend between the first side of the substrate andthe second side of the substrate, each of the perforations being alignedwith a respective one of the channels. Each of these gas exchange unitsalso includes (c) a blood inlet configured to supply blood to the firstside of the substrate, wherein the blood inlet is in fluid communicationwith the perforations such that blood that arrives via the blood inletwill flow through the perforations and continue on through the channels,and (d) a blood outlet configured to accept blood that arrives from theoutflow end of the channels. This gas exchanger also includes a housingconfigured to house the plurality of gas exchange units. The housing hasa gas inlet configured to route a gas into the spaces between thenanotubes, and a gas outlet configured to route the gas away from thespaces between the nanotubes. This gas exchanger also includes a bloodinflow path configured to route incoming blood to at least one of thegas exchange units, and a blood outflow path configured to routeoutgoing blood from at least one of the gas exchange units.

In some embodiments, the gas exchange units are interconnected so thatthe blood flows through the gas exchange units in series. In someembodiments, in each of the gas exchange units, each of the nanotubes isperpendicular to the substrate, each of the channels is perpendicular tothe substrate, each of the channels has a diameter between 2 and 500 nm,and the nanotubes have a diameter between 5 and 20 nm. In someembodiments, in each of the gas exchange units, the nanotubes aredisposed on the substrate in an array configuration, with a plurality ofvoids in the array, with each of the voids corresponding to a respectivechannel. In some embodiments, the gas exchange units are interconnectedso that the blood flows through the gas exchange units in parallel.

Another aspect of the invention is directed to a method for processingblood that includes blood cells and plasma. This method includes thesteps of providing a plurality of blood flow channels that aresurrounded by nanotubes, each of the channels having an inflow end andan outflow end. Each of the channels is wide enough for the blood toflow through, and the nanotubes are spaced close enough to each other toretain the plasma within the channels when the blood is flowing throughthe channels. This method also includes the steps of passing bloodthrough the through the channels, and passing a gas through the spacesbetween the nanotubes outside the blood flow channels, wherein the gasinteracts with the blood in the channels.

In some embodiments, each of the channels has a diameter between 2 and500 nm. In some embodiments, the nanotubes have a diameter between 5 and20 nm. In some embodiments, the nanotubes are spaced on centers that arebetween 1.5 times the diameter of the nanotubes and 5 times the diameterof the nanotubes.

Another aspect of the invention is directed to an apparatus thatincludes a substrate having a first side and a second side. A pluralityof nanotubes are disposed on the second side of the substrate withspaces between the nanotubes, and the nanotubes are disposed on thesubstrate in a configuration that leaves a plurality of fluid flowchannels that are surrounded by the nanotubes. Each of the channels hasan inflow end and an outflow end, each of the channels is wide enoughfor a fluid to flow through, and the nanotubes are spaced close enoughto each other to retain the fluid within the channels when the fluid isflowing through the channels. The substrate has a plurality ofperforations that extend between the first side of the substrate and thesecond side of the substrate, each of the perforations being alignedwith a respective one of the channels. This apparatus also includes afluid inlet configured to supply fluid to the first side of thesubstrate. The fluid inlet is in fluid communication with theperforations such that fluid that arrives via the fluid inlet will flowthrough the perforations and continue on through the channels. It alsoincludes a fluid outlet configured to accept fluid that arrives from theoutflow end of the channels, and a housing configured to house thesubstrate and the array of nanotubes. The housing has a gas inletconfigured to route a gas into the spaces between the nanotubes and agas outlet configured to route the gas away from the spaces between thenanotubes.

In some embodiments, each of the nanotubes is perpendicular to thesubstrate and each of the channels is perpendicular to the substrate. Insome embodiments, the nanotubes are disposed on the substrate in anarray configuration, with a plurality of voids in the array, whereineach of the voids corresponds to a respective channel.

Another aspect of the invention is directed to an apparatus thatincludes a plurality of units. Each of the units includes (a) asubstrate having a first side and a second side, and (b) a plurality ofnanotubes disposed on the second side of the substrate with spacesbetween the nanotubes. The nanotubes are disposed on the substrate in aconfiguration that leaves a plurality of fluid flow channels that aresurrounded by the nanotubes, each of the channels having an inflow endand an outflow end. Each of the channels is wide enough for a fluid toflow through, and the nanotubes are spaced close enough to each other toretain the fluid within the channels when the fluid is flowing throughthe channels. The substrate has a plurality of perforations that extendbetween the first side of the substrate and the second side of thesubstrate, each of the perforations being aligned with a respective oneof the channels. Each of the units also includes (c) a fluid inletconfigured to supply fluid to the first side of the substrate, whereinthe fluid inlet is in fluid communication with the perforations suchthat fluid that arrives via the fluid inlet will flow through theperforations and continue on through the channels, and (d) a fluidoutlet configured to accept fluid that arrives from the outflow end ofthe channels. The apparatus also includes a housing configured to housethe plurality of units, the housing having a gas inlet configured toroute a gas into the spaces between the nanotubes, and a gas outletconfigured to route the gas away from the spaces between the nanotubes.The apparatus further includes a fluid inflow path configured to routeincoming fluid to at least one of the units and a fluid outflow pathconfigured to route outgoing fluid from at least one of the units.

In some embodiments, the units are interconnected so that the fluidflows through the units in series. In some embodiments, in each of theunits, each of the nanotubes is perpendicular to the substrate, each ofthe channels is perpendicular to the substrate, each of the channels hasa diameter between 2 and 500 μm, and the nanotubes have a diameterbetween 5 and 20 nm. In some embodiments, in each of the units, thenanotubes are disposed on the substrate in an array configuration, witha plurality of voids in the array, with each of the voids correspondingto a respective channel. In some embodiments, the units areinterconnected so that the fluid flows through the units in series.

Another aspect of the invention is directed to a method for interactinga fluid with a gas. This method includes the step of providing aplurality of fluid flow channels that are surrounded by nanotubes, eachof the channels having an inflow end and an outflow end, wherein each ofthe channels is wide enough for a fluid to flow through, and wherein thenanotubes are spaced close enough to each other to retain the fluidwithin the channels when the fluid is flowing through the channels. Thismethod also includes the steps of passing fluid through the through thechannels and passing a gas through the spaces between the nanotubesoutside the fluid flow channels, wherein the gas interacts with thefluid in the channels.

In some embodiments, each of the channels has a diameter between 2 and500 nm. In some embodiments, the nanotubes have a diameter between 5 and20 nm. In some embodiments, the nanotubes are spaced on centers that arebetween 1.5 times the diameter of the nanotubes and 5 times the diameterof the nanotubes. In some embodiments, the interaction between the gasand the fluid in the channels comprises an exchange of gasses. In someembodiments, the interaction between the gas and the fluid in thechannels comprises an exchange of heat.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A depicts a single wall nanotube made of carbon.

FIG. 1B is a scanning electron microscope photo of a matrix of parallelaligned carbon nanotubes.

FIG. 2A is a schematic representation of a gas exchanger that has twogas exchange units of a first type connected in series.

FIG. 2B is a schematic representation of a gas exchanger that has twogas exchange units of a second type connected in series.

FIG. 3A depicts a preferred way to lay out the nanotubes for the FIG. 2Bembodiment.

FIG. 3B depicts a preferred way to lay out the nanotubes for the FIG. 2Aembodiment.

FIG. 3C depicts another preferred way to lay out the nanotubes for theFIG. 2B embodiment.

FIG. 3D is a detailed view of FIG. 3A.

FIG. 4A is a more detailed representation of a single gas exchange unitof the FIG. 2B embodiment.

FIG. 4B is a magnified view of a region of FIG. 4A.

FIG. 5 depicts a gas exchanger with ten gas exchange units connected inparallel.

FIGS. 6A, 6B, and 6C depict three ways how a gas exchanger can be usedas an artificial lung.

FIG. 7 is a schematic representation of how a gas exchanger can be usedas a respiratory assist device.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention relates to a Gas Exchanger (“GE”) that will bedescribed here within the framework of an artificial lung for efficientgas exchange (O₂, CO₂, etc.) between compartments such as human (oranimal) blood and ambient air or some other gas. The main examplesdescribed herein are an artificial lung and respiratory aid based on astructure made of nanotubes.

The GE system contains one or more gas exchange units 110 (GEU), andFIG. 2A is a schematic representation of two such GEUs connected inseries. Each GEU 110 includes a matrix of parallel aligned Blood FlowChannels 2 (“BFC”). FIG. 2A schematically depicts a first set 20 of fourparallel BFCs in one GEU on the left, and a second set 20′ of fourparallel BFCs in a second GEU on the right, with the first GEU connectedin series with the second GEU. Note that while FIG. 2A schematicallydepicts only four parallel BFCs in each GEU, in practice there will bemany more BFCs in each GEU. For example, if the BFCs are 20 μm indiameter and are spaced on 40 μm centers, 62,500 BFCs would fit in a 1cm² area. Note also that while FIG. 2A depicts two GEUs in series, thatnumber may vary, and a given GE could have more than two GEUs in series,or only a single GEU. In alternative embodiments, a plurality of GEUsmay be connected in parallel instead of in series.

Each BFC is surrounded by Nanotubes, which are shown in FIG. 3B (but notshown in FIG. 2A). FIG. 3B depicts a preferred way to lay out the NTs todefine the BFCs for the FIG. 2A embodiment, with the NTs laid out in afield pattern. The view depicted in FIG. 3B is a cross section throughthe BFCs and the NTs, and there are voids in the field of NTs thatdefine the BFCs 2. In some embodiments, the diameter of the voids isbetween 2 and 500 μm, and in some embodiments the diameter is between 5and 20 μm. (Note that all the figures in this application are not drawnto scale). The NTs within the field (i.e., outside the voids) arepreferably arranged as a two dimensional matrix. The NTs preferably havediameters in the order of 1-100 nm, more preferably between 5 and 20 nm,and still more preferably between 10 and 20 nm. The optimum distancebetween the NT centers will be related to the NT diameter, so that theNTs do not end up too far away from each other. More specifically, whenthinner NTs are used, the NTs should preferably be packed more closelytogether. Preferably, the spacing between NTs will be not more than afew diameters of the NTs, and will more preferably be on the order of 1diameter. For example, if NTs with 10 nm diameter are used, the NTswould preferably be spaced on centers of about 20 nm, which would meanthat the spacing between adjacent NTs would be around one diameter. Butif NTs with 20 nm diameter are used, the NTs would preferably be spacedfurther apart, on centers of about 40 nm. A suitable relationshipbetween the NT diameter and the NT spacing is to space the NTs oncenters that are between 1.5 times the diameter of the NT and 5 timesthe diameter of the NT. For example, if NTs with a diameter of 10 nm areused, the NTs should preferably be spaced on centers between 15 and 50nm. In less preferred embodiments, the NTs are spaced centers between 1times and 10 times the diameter of the NTs, or even between 0.5 timesand 20 times the diameter of the NTs. Note that the NT packing ordensity affects the resistance to flow of the gas through the “forest”of NTs, which is an additional consideration that may be adjusteddepending on the specific need.

Methods for fabricating large masses of parallel carbon NTs, as depictedin FIG. 1B, were described by Li et al. in Highly-Ordered CarbonNanotube Arrays for Electronics Applications, Applied Physics Letters(1999); 75, 367-369. The desired placement of the NTs can be achieved bypositioning the NTs at the desired locations using standard techniques.For example, the NTs may be fabricated on a substrate (which serves as aNT base) at the desired position using a lithography-based process. Thismay be accomplished by depositing catalysts on a substrate that has beenmasked to create the desired pattern, and then exposing it to carbongas. The carbon from the gas then forms NTs (by self-assembly) on thespots where the catalyst has been deposited. NTs will not grow on theother parts of the substrate.

Returning to FIG. 2A, blood flows through the depicted device from leftto right, in the blood flow direction 107. Blood that originates fromthe person's blood circulation flows through the Inflow channel 106 intoan initial blood pool 105 that is bounded by a support 100 on the left,by the first NT base 120 on the right, and by casing 111 in directionsthat are perpendicular to the blood flow direction 107. In alternativeembodiments, the boundary of the blood pool in directions that areperpendicular to the blood flow direction 107 can be implemented usingan appropriate ring enclosure. The width of the initial blood pool isd1, and a suitable dimension for d1 is between 0.1-4 mm. However, anydistance d1 that permits blood flow without adding a significantresistance to flow can be used instead.

The NT base 120 is preferably the substrate on which the NTs thatsurround the BFCs were fabricated, and the NT base 120 should have ahole or perforation 104 located at the center of each BFC. The NTsextend to the right from the NT base 120 and span a distance d2 todefine the BFCs, which are oriented parallel to the direction of bloodflow 107 and perpendicular to the gas flow direction 108. In somepreferred embodiments, the distance d2 is between 0.1-1 cm. Because theNTs are grown on the NT base 120 and remain attached to it, no leakagenear the base is expected. The NTs are held firmly in place by theextremely strong Wan der Vaals forces characterizing such nm scalestructures. As a result of this configuration, blood that flows into thepool 105 will flow to the right through the perforations 104 in the NTbase 120 and continue towards the right into and through the first set20 of BFCs 2 in the first GEU.

A second NT base 120 is preferably positioned a short distance (e.g.,between 0.1-4 mm in some embodiment or between 0.5 and 2 mm in someembodiments) away from the right end of the NTs that define the firstset 20 of BFCs 2. When blood exits the first set of BFCs, it will flowinto the gap between (a) the right end of the NTs that define the firstset 20 of BFCs 2 and (b) the second NT base 120. The second GEU has asecond set 20′ of BFCs 2 that is similar in construction to the firstset 20 of BFCs 2, each BFC having an aligned perforation 104 in the NTbase. The blood that enters the gap will then flow to the right throughthe perforations 104 in the second NT base 120 and continue towards theright, into and through the second set 20′ of BFCs 2 in the second GEU.

Note that when the blood exits the first set 20 of BFCs 2 and flows intothe gap, surface tension of the blood (which is a water-based liquid)together with the hydrophobicity of the carbon NTs should prevent theblood from backing up into the very small spaces between the NTs thatform the first set 20 of BFCs 2. Instead, the blood should flow to theright into the second set 20′ of BFCs 2 in the second GEU, because thediameter of the BFCs in the second GEU is orders of magnitude largerthan the very small spaces between the NTs in the first GEU. The bloodwould then flow according to the pressure gradient through the secondGEU (i.e., in the blood flow direction 107 through the holes in thesecond NT base 120 and then through the second set 20′ of BFCs 2 in thesecond GEU) rather than backwards. Note that the distance betweenadjacent NTs (i.e., less than a few diameters of the NTs, and preferablyon the order of 1 diameter) is low enough to prevent blood plasma (orwater) from penetrating the space between the NTs due to surfacetension.

In alternative embodiments, additional stages (not shown) may be addedin series. The blood eventually reaches the last GEU. A final support100 is preferably positioned a short distance (e.g., between 0.1-4 mm insome embodiments, or between 0.5 and 2 mm in some embodiments) away fromthe right end of the NTs that define the last set 20′ of BFCs 2. Whenblood exits the last set of BFCs, it will flow into the gap between (a)the right end of the NTs that define the last set 20′ of BFCs 2 and (b)the final support 100. From there it will flow into the blood outflowchannel 118.

While the blood is in the BFCs 2 in any of the stages, the blood has achance to interact with the gases in the gas flow region 101. Thesegases flow in a gas flow direction 108 (i.e., up in FIG. 2A) that ispreferably perpendicular to the direction of blood flow 107 (i.e., tothe right in FIG. 2A). At the end of this process the blood continuesthrough outflow channel 118, back to the blood circulation. It isimportant to note that the BFCs have no coating or membrane to keep theblood from escaping the BFC. However, due to the high density of thehydrophobic NTs surrounding the BFCs and the high surface tension ofwater, when a water-based fluid, such as blood, occupies or flows in theBFC, it will not leak out of the BFCs into the gas flow region 101. Inother words, the NTs surrounding the BFC form a virtual boundary for theliquid flow.

Casing 111, a rigid biocompatible housing, seals the initial Blood Pool105 as well as the one or more GEUs 110 contained within the casing 111.This permits gas exchange between the blood in the BFC and the air (orother gases) in the gas flow regions 101.

FIG. 2B depicts an alternative embodiment that is similar to the FIG. 2Aembodiment, except that additional blood pools 105 are added betweenadjacent GEU stages. In this embodiment, blood exiting one GEU iscollected into a blood pool 105 confined between a planar support 100(on the left) and the subsequent NT base 120 before it enters the nextGEU. The planar support 100 for each GEU stage has holes or perforations104 that are aligned to the position of the BFCs 2 of the previous stageGEU (except for the input of the first stage and the output of the laststage, which preferably each have a single larger port). For any givenstage, the distance between the planar support 100 and the subsequent NTbase 120 is d1, and a suitable dimension for d1 is between 0.1-4 mm.However, any separation that permits blood flow without adding asignificant resistance to flow can be used instead. Casing 111, a rigidbiocompatible housing, seals all the Blood Pools 105 as well as all theGEUs 110 contained within the casing 111.

In this FIG. 2B embodiment, the NTs may be laid out as shown in FIG. 3B,which is discussed above. But alternative layouts for the NTs may alsobe used in this embodiment.

FIG. 3A depicts a first alternative approach for laying out the NTs todefine the BFCs in the FIG. 2B embodiment. In this approach, the NTs arelaid out in pattern of rings 1 so that the inner boundary of each ring 1defines a BFC 2. The depicted view is a cross section through the BFCsand the NTs. The diameter of the inner boundary of the ring is between 2and 500 μm in some embodiments, and between 5 and 20 μm in someembodiments. In this approach, the thickness of each ring (i.e., thedistance between the innermost NTs of the ring and the outermost NTs ofthe ring) is preferably between 100 nm and 10 μm, and the NTs within thering are preferably spaced on centers between 10 and 100 nm. As in theFIG. 3B approach, the distance between the NT centers is preferablyrelated to the NT diameter, so that the NTs do not end up too far awayfrom each other. FIG. 3D is a detailed view of a ring 1 and the BFC 2 ofFIG. 3A. The NTs in the ring 1 may be laid out in a two dimensionalmatrix, as shown in FIG. 3D, or in any other layout that maintainsappropriate spacing between the centers of the NTs.

FIG. 3C depicts a second alternative approach to lay out the NTs todefine the BFCs in the FIG. 2B embodiment. The depicted view is a crosssection through the BFCs and the NTs. This approach is similar to theapproach depicted in FIG. 3A, except that additional NTs are added toprovide structural support. The additional NTs may be configured to formsupport bridges 117, as shown in FIG. 3C, but alternative layouts forthe additional NTs may be used instead. Examples of such alternativelayouts (not shown) include stripes and grids. The layout of theadditional NTs may be selected to provide structural strength withoutunduly increasing the resistance to air flow. Another example (notshown) would be to add clusters of NTs at midpoints between adjacentBFCs, arranged in a column-like fashion to add structural support. Forexample, a set of NTs arranged to fill in a circle with a diameter of 10μm, with the NTs in the set spaced on centers between 10 and 100 nm,could serves as a support column. Each NT in such a support column wouldhave the same length d2 as the NTs in the rings that surround the BFCs.

For all of the embodiments described above, the blood in the inflowchannel 106 is preferably venous blood that is low in oxygen and rich inCO₂. The two blood gases undergo an exchange with the gas flowing in thegas flow region 101 around the BFCs in a direction 108 that ispreferably normal to that of the BFC blood flow 107. This incoming gasis preferably rich in oxygen and has a low or zero concentration of CO₂so that the gas exchange is by diffusion along the concentrationgradients. The blood in the outflow channel 118 will then be richer inO₂ than the incoming blood.

The efficacy of the gas exchange is a function of the area of contactbetween the flowing blood and the flowing gas that may be oxygen or air.As mentioned above, in a normal pair of lungs this contact surface areais typically about 70 m² while the blood flow is 5-7 L/min and air flowis similar. The amount of Oxygen or CO₂ exchanged in normal human lungsis typically 200-250 cm³/min.

Let us now compute the parameters of gas exchange that satisfy thenormal physiological requirements: The total BFC surface area that isneeded for the gas exchange is a direct function of the BFC diameter andpacking, i.e. the distance between the BFCs, and the total number ofBFCs in the GE volume. For a GE having a total volume of 2 liters (e.g.,10 cm×10 cm×20 cm), the surface area available for exchange isindependent of the arrangement of the GEUs within the GE, i.e. in seriesor in parallel, or their spatial configuration. For such a GE, if weassume that the BFC Radius is 10 μm, and the center-to-center distanceof the BFCs is 40 μm, the total gas-blood exchange area is close about80 m², which is approximately equal to a typical pair of lungs. TheDiffusion Capacity will therefore be over 2000 cm³ O₂ per min (whichexceeds the requirement of 250 cm³/min), and the Blood volume will beabout 400 cm³ (which is comparable to that of the adult humanrespiratory system).

FIG. 4A is a more detailed representation of a single GEU 110 of theFIG. 2B variety, in which the NTs are arranged in rings 1 (as shown inFIGS. 3A and 3D). The GEU 110 has a set of parallel BFCs located betweena first support 100 and a first NT base 120 on the left and a pair ofsupports 100 on the right. The O₂ rich gas flows into the gas inlet 116,flows past the BFCs 2, and exits the gas outlet 114. As the gas flowspast the BFCs 2, it comes in contact with the blood in the BFCs so thatgases can be exchanged. 4A-1 is a cross section through the firstsupport 100, which shows the holes in the support, and 4A-2 is a crosssection through a set of BFCs 2. The holes in the NT base 120 line upwith the BFCs, as best seen in FIG. 4B, which is a magnified view of theregion 4A-3 of FIG. 4A. The holes in the support 100 also line up withthe BFCs of the previous stage, as best seen in FIG. 4B. Note thatalthough FIG. 4A schematically shows only 22 BFCs, there will in fact bemany more BFCs that are spaced much more closely together, as describedabove.

The overall GE preferably includes a plurality of GEUs connectedtogether. The GEUs may be connected in series or in parallel to form theGE. Since connecting GEUs in series will increase the flow resistance,the number of GEUs that are connected in series should preferably belimited (e.g., to not more than ten). The GEUs may also be connected ina series/parallel combination. For example, three GEUs may be connectedin series, and then the resulting set of three GEUs may be connected inparallel with five similar sets of three series-connected GEUs.Different series/parallel combinations may also be used.

The number of GEUs that are used in any given GE may vary, depending onthe required surface area for diffusion. In some embodiments, a GE maycontain between 2 and 20 GEUs connected in series, or between 2 and 10GEUs connected in series.

Optionally, a plurality of GEUs may be combined into subsystems, andthose subsystems may be connected in series, in parallel, or inseries/parallel combinations to form the overall GE. When the BFCs are20 μm in diameter and are spaced on 40 μm centers, 62,500 BFCs would fitin a 1 cm² area, and would impose resistance to flow through the BFCs of1.63·10⁵ g/(s cm⁴). One example of suitable dimensions for a subsystemfor use in a GE would be a width of 10 cm, a height of 10 cm, and athickness of about 1.1 cm. The 1.1 cm thickness could be made of 10 GEUsthat are each 0.1 cm thick, arranged in series as depicted in FIG. 2A,separated by 9 NT bases 120 that are each 0.1 mm thick between the GEUs,plus an additional blood pool 105 at each end. These 10×10×1.1 cmsubsystems can then be configured in parallel to make the complete GE.FIG. 5 depicts ten such subsystems 200 connected in parallel. When 20such subsystems are arranged in parallel, resistance to flow will besufficiently low so that less than 50 mmHg is required to induce therequired 5-7 L/min blood flow (for subsystems of 10 cm×10 cm×1.1 cm eachwith the BFC diameter and spacing described above). The Dwell Time(i.e., the time flowing blood is exposed to gas exchange when flowingfrom input to output) for this configuration will be over 1 sec, whichis well above the required minimal value of 0.2-0.4 sec.

In alternative configurations, the subsystems may be smaller e.g., 2 cmwide, 2 cm high, and about 1 cm thick, with similar internalconstruction to the 20×20×1.1 cm subsystems described above. These 2×2×1cm subsystems can then be configured in parallel and/or in series toform the complete GE. In other alternative embodiments, the subsystemsmay be larger (e.g., 20 cm wide, 20 cm high, and about 2 cm thick).

Yet another possible configuration of GEUs for forming a GE would be toconnect 2000 1 cm² units in parallel into a subsystem, and then connect10 such subsystems in series. In such a GE system, the surface area ofoxygen diffusion is sufficient for physiological quiet breathing and theresistance to flow in the BFCs would be only 815 g/(s cm⁴). Thisconfiguration would also have a pressure drop of less than 50 mmHg when5-7 L/min of blood is flowing through the system.

Note that the diffusion capacity of the GEs discussed herein can be evenhigher than human lungs in which a 0.5-1 μm membrane (made up of livingcells and a basal membrane) is interposed between the air and blood. Incontrast, there is a direct air-blood contact in the GE. The continuousgas flow around the BFCs in the GE is also more efficient than thein/out air flow in the lungs during natural respiration.

We turn next to the efficacy of the Gas Exchanger with regards to CO₂.The water Diffusion coefficients of CO₂ and O₂ are similar while thesolubility of CO₂ is about 24 times higher than that of O2. As the O₂and CO₂ concentration difference between oxygenated and reduced bloodare similar, the diffusion rate of CO₂ is about 20 times that of O₂.Thus, the CO₂ transport in all the above processes is expected to besuperior to that of O₂.

Two examples of clinical applications are using the GE as an artificiallung and using the GE as a respiratory assist device.

FIGS. 6A, 6B, and 6C depict how a GE 75 can be used as an artificiallung, in which case the GE 75 replaces either one or both lungs. In thisapplication, the GE may be implanted (as shown in FIGS. 6B and 6C) orexternal (as shown in FIG. 6A). In either case, the blood enters the GE75 via tubing 73 from the pulmonary artery 71 and the blood is returnedto the pulmonary vein 72 from the GE via tubing 73. Air or oxygen can bepumped into the GE 75 via the gas input tube 77 by pump 76 and theexhaust leaves via the exhaust tube 78, as shown in FIGS. 6A and 6B.

Alternatively, air can be driven through the trachea and main bronchivia natural breathing as shown in FIG. 6C. In this case the air flows intube 80 from the bronchi into the GE 75 that is connected via tube 81 toan expandable gas bag 82, which inflates and deflates, i.e. changesvolume during inspiration and expiration, respectively. Tubes 80 and 81serve also as the exhaust tubes for the gas exiting the bag 82 via theGE 75 back into the main bronchi and environment.

In any of these embodiments, the blood flow can be maintained by thenatural pressure generated by the right ventricle or an appropriateblood vessel. Alternatively it can be driven by an external or implantedpump designed to generate blood flow for long periods of time. Suchpumps are commercially available. The blood exiting the GE is returnedto the body via a pulmonary vein 72 or veins, or any other appropriateblood vessel.

The flow rates for both blood and air are preferably adjustable to matchthe needs of the person, etc. this adjustment may be dynamic accordingto the changing need, for example during exercise. The adjustment may becontrolled by sensors of a relevant physiological parameter such as thepartial pressure of O₂ and/or CO₂ in the blood, Hb O₂ saturation(oximetry), pH, etc. To supply the O₂ (or other gas) needs, which amountto approximately 250 cm³/min for a resting adult man, a flow of about5-7 L/min oxygenated blood is required; and this may need to beincreased by a factor of up to 4-5 during exercise. An additional factorthat should preferably be taken into consideration is the time theflowing blood is exposed to the gas diffusion process, the dwell time.In the normal resting human lung this duration is about ⅓-⅕ of a secwhile the flow velocity is usually under 100 cm/s. The blood flow in theGE is compatible with these requirements. When the subject's heart ishealthy, the blood flow may be powered by the patient's heart. Note thatthe series/parallel configuration of GEUs within the GE may be selectedin advance to provide a desired flow resistance. To increase theresistance, the number of GEUs connected in series should be increased.To decrease the resistance, the number of GEUs connected in seriesshould be reduced, and the number of parallel connections should beincreased.

The corresponding air (or oxygen) flow is also about 5-8 L/min at restand up to 5 times larger during exercise. When implanted, the Gas inlet116 and Gas Outlet 114 (shown in FIG. 4) can be connected to thepatient's bronchial system as shown in FIG. 6C and flow can bemaintained by respiratory movements or a by an appropriate pump. Whenthe GE is external (as shown in FIG. 6A) or implanted without the use ofthe respiratory ventilation ability (FIG. 6B), the gas Inlet & Outletare preferably in communication with the ambient air or a gas reservoirthrough appropriate filters. In this case, gas flow can be continuouslydriven by an appropriate pump and regulated by appropriate sensors.

FIG. 7 is a schematic representation of how the GE can be used as arespiratory assist device, in order to provide additional oxygenation ofblood for a patient with a failing respiratory system. In these casesthe GE 300 is positioned externally, as shown, or implanted. In thisapplication, the blood flowing through the GE is preferably derived herefrom a large blood vessel, for example the femoral vein. The bloodexiting the GE can be introduced back into the femoral vein or veins, orany other appropriate blood vessel.

Note that the embodiments described above are described using nanotubes.In alternative embodiments, the nanotubes described above may bereplaced with other species of hydrophobic pillar-shaped structures withdiameters between 1 and 100 nm. For example, in some embodiments,hydrophobic nanofibers, nanorods, or nanowires with diameters between 1and 100 nm may be used in place of the nanotubes described above.

The invention is described above in the context of delivering O₂ toblood and removing CO₂ from blood. But the invention is not limited tothat application, and can be used to deliver other gases to blood. Forexample, it may be used in connection with a body part that has adedicated circulation (such as a leg, brain, kidney) to deliver anydesired gas to that body part. This can be used to deliver a chemicalsuch as an anesthetic or therapeutic gas intended to act locally. Insuch a case the gas will be inputted into the artery and outputted(eliminated) via the vein, etc.

Note that in other types of GEs, fluids other than blood may beutilized. The invention is also not limited to medical uses, and can beused to exchange gases in other types of fluid flow systems, includingindustrial applications.

As additional use of the apparatuses described above is as a heatexchanger. Regardless of whether any gases are exchanged between the gasand liquid that flow through the device, heat transfer can still occurbetween the gas and the fluid. As a result, hot fluid can be used toheat the gas, cold fluid can be used to cool the gas, hot gas can beused to heat the fluid, or cold gas can be used to cool the fluid. Theheat transfer is expected to be very effective relative to prior artdevices because the contact surface area is very large, and there is nophysical barrier between the gas and the fluid. Optionally, sensors andpumps may be used to control the exchange so as to maintain the desiredtemperature. These sensors and pumps may also be used when the primarypurpose is gas exchange, as in the embodiments described above.

While the present invention has been disclosed with reference to certainembodiments, numerous modifications, alterations, and changes to thedescribed embodiments are possible without departing from the sphere andscope of the present invention, as defined in the appended claims.Accordingly, it is intended that the present invention not be limited tothe described embodiments, but that it has the full scope defined by thelanguage of the following claims, and equivalents thereof.

I claim:
 1. A gas exchanger apparatus comprising: a substrate having afirst side and a second side; a plurality of hydrophobic pillar-shapedstructures with diameters between 1 and 100 nm disposed on the secondside of the substrate with spaces between the pillar-shaped structures,wherein the pillar-shaped structures are disposed on the substrate in aconfiguration that leaves a plurality of fluid flow channels that aresurrounded by the pillar-shaped structures, each of the channels havingan inflow end and an outflow end, wherein each of the channels is wideenough for a fluid to flow through, and wherein the pillar-shapedstructures are spaced close enough to each other to retain the fluidwithin the channels when the fluid is flowing through the channels, andwherein the substrate has a plurality of perforations that extendbetween the first side of the substrate and the second side of thesubstrate, each of the perforations being aligned with a respective oneof the channels; a fluid inlet configured to supply fluid to the firstside of the substrate, wherein the fluid inlet is in fluid communicationwith the perforations such that fluid that arrives via the fluid inletwill flow through the perforations and continue on through the channels;a fluid outlet configured to accept fluid that arrives from the outflowend of the channels; and a housing configured to house the substrate andthe array of pillar-shaped structures, the housing having a gas inletconfigured to route a gas into the spaces between the pillar-shapedstructures and a gas outlet configured to route the gas away from thespaces between the pillar-shaped structures.
 2. The gas exchangerapparatus of claim 1, wherein each of the pillar-shaped structures isperpendicular to the substrate and wherein each of the channels isperpendicular to the substrate.
 3. The gas exchanger apparatus of claim1, wherein the pillar-shaped structures are disposed on the substrate inan array configuration, with a plurality of voids in the array, whereineach of the voids corresponds to a respective channel.
 4. The gasexchanger apparatus of claim 1, wherein each of the channels has adiameter between 2 and 500 μm.
 5. The gas exchanger apparatus of claim1, wherein the pillar-shaped structures have a diameter between 5 and 20nm.
 6. The gas exchanger apparatus of claim 1, wherein the pillar-shapedstructures are spaced on centers that are between 1.5 times the diameterof the pillar-shaped structures and 5 times the diameter of thepillar-shaped structures.
 7. The gas exchanger apparatus of claim 1,wherein each of the pillar-shaped structures is perpendicular to thesubstrate, each of the channels is perpendicular to the substrate, eachof the channels has a diameter between 2 and 500 μm, and thepillar-shaped structures have a diameter between 5 and 20 nm.
 8. The gasexchanger apparatus of claim 7, wherein the pillar-shaped structures arespaced on centers that are between 1.5 times the diameter of thepillar-shaped structures and 5 times the diameter of the pillar-shapedstructures.
 9. The gas exchanger apparatus of claim 8, wherein thepillar-shaped structures are disposed on the substrate in an arrayconfiguration, with a plurality of voids in the array, wherein each ofthe voids corresponds to a respective channel.
 10. The gas exchangerapparatus of claim 1, wherein the pillar-shaped structures arenanotubes.
 11. The gas exchanger apparatus of claim 1, wherein thepillar-shaped structures are nanorods.
 12. A gas exchanger apparatuscomprising: a plurality of units, each of the units including (a) asubstrate having a first side and a second side, (b) a plurality ofhydrophobic pillar-shaped structures with diameters between 1 and 100 nmdisposed on the second side of the substrate with spaces between thepillar-shaped structures, wherein the pillar-shaped structures aredisposed on the substrate in a configuration that leaves a plurality offluid flow channels that are surrounded by the pillar-shaped structures,each of the channels having an inflow end and an outflow end, whereineach of the channels is wide enough for a fluid to flow through, andwherein the pillar-shaped structures are spaced close enough to eachother to retain the fluid within the channels when the fluid is flowingthrough the channels, and wherein the substrate has a plurality ofperforations that extend between the first side of the substrate and thesecond side of the substrate, each of the perforations being alignedwith a respective one of the channels, (c) a fluid inlet configured tosupply fluid to the first side of the substrate, wherein the fluid inletis in fluid communication with the perforations such that fluid thatarrives via the fluid inlet will flow through the perforations andcontinue on through the channels, and (d) a fluid outlet configured toaccept fluid that arrives from the outflow end of the channels; ahousing configured to house the plurality of units, the housing having agas inlet configured to route a gas into the spaces between thepillar-shaped structures, and a gas outlet configured to route the gasaway from the spaces between the pillar-shaped structures; a fluidinflow path configured to route incoming fluid to at least one of theunits; and a fluid outflow path configured to route outgoing fluid fromat least one of the units.
 13. The gas exchanger apparatus of claim 12,wherein the units are interconnected so that the fluid flows through theunits in series.
 14. The gas exchanger apparatus of claim 12 wherein, ineach of the units, each of the pillar-shaped structures is perpendicularto the substrate, each of the channels is perpendicular to thesubstrate, each of the channels has a diameter between 2 and 500 μm, andthe pillar-shaped structures have a diameter between 5 and 20 nm. 15.The gas exchanger apparatus of claim 12 wherein, in each of the units,the pillar-shaped structures are disposed on the substrate in an arrayconfiguration, with a plurality of voids in the array, with each of thevoids corresponding to a respective channel.
 16. The gas exchangerapparatus of claim 12, wherein the units are interconnected so that thefluid flows through the units in series.
 17. A method for interacting afluid with a gas, the method comprising the steps of: providing aplurality of fluid flow channels that are surrounded by hydrophobicpillar-shaped structures with diameters between 1 and 100 nm, each ofthe channels having an inflow end and an outflow end, wherein each ofthe channels is wide enough for a fluid to flow through, and wherein thepillar-shaped structures are spaced close enough to each other to retainthe fluid within the channels when the fluid is flowing through thechannels; passing fluid through the through the channels; and passing agas through the spaces between the pillar-shaped structures outside thefluid flow channels, wherein the gas interacts with the fluid in thechannels.
 18. The method of claim 17, wherein each of the channels has adiameter between 2 and 500 μm.
 19. The method of claim 17, wherein thepillar-shaped structures have a diameter between 5 and 20 nm.
 20. Themethod of claim 17, wherein the pillar-shaped structures are spaced oncenters that are between 1.5 times the diameter of the pillar-shapedstructures and 5 times the diameter of the pillar-shaped structures. 21.The method of claim 17, wherein the interaction between the gas and thefluid in the channels comprises an exchange of gasses.
 22. The method ofclaim 17, wherein the interaction between the gas and the fluid in thechannels comprises an exchange of heat.